PMID- 33512755 OWN - NLM STAT- MEDLINE DCOM- 20210709 LR - 20221207 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 6 DP - 2021 Jun TI - A randomized, placebo-controlled study to evaluate the efficacy and safety of adding omarigliptin to insulin therapy in Japanese patients with type 2 diabetes and inadequate glycaemic control. PG - 1242-1251 LID - 10.1111/dom.14331 [doi] AB - AIM: To evaluate the efficacy and safety of adding the once-weekly oral dipeptidyl peptidase-4 inhibitor omarigliptin to treatment of Japanese patients with type 2 diabetes and inadequate glycaemic control on insulin monotherapy. MATERIALS AND METHODS: In a 52-week clinical trial, Japanese patients on insulin monotherapy were randomized to once-weekly omarigliptin 25 mg (N = 123) or placebo (N = 61) for a 16-week, double-blind, placebo-controlled period. After Week 16, patients continued or switched to omarigliptin for a 36-week open-label period. RESULTS: From a mean baseline of approximately 8.8%, the Week 16 least squares mean changes in HbA1c were -0.61% (omarigliptin) and 0.29% (placebo); the between-group difference was -0.90% (p < .001). At Week 52, the mean change from baseline in HbA1c was -0.57% in both the group on omarigliptin for 52 weeks and the group on omarigliptin for 36 weeks (switched from placebo at Week 16). During the first 16 weeks of treatment, the incidences of adverse events (AEs), serious AEs, drug-related AEs and discontinuation from trial medication because of an AE were similar in both groups. A slight increase in incidence of symptomatic hypoglycaemia was observed in the omarigliptin group (n = 13 [10.6%]) compared with placebo (n = 4 [6.6%]). No severe hypoglycaemia was reported during the study. No new safety signals emerged with treatment beyond Week 16 through Week 52. CONCLUSION: The addition of once-weekly omarigliptin to insulin therapy for up to 52 weeks was generally well tolerated and provided clinically meaningful improvement in glycaemic control throughout the trial period. ClinicalTrials.gov: NCT02906709. CI - (c) 2021 Merck Sharp & Dohme Corp. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Toranomon Hospital, Tokyo, Japan. FAU - Seino, Yutaka AU - Seino Y AD - Kansai Electric Power Hospital, Osaka, Japan. AD - Kansai Electric Power Medical Research Institute, Osaka, Japan. FAU - Kaku, Kohei AU - Kaku K AUID- ORCID: 0000-0003-1574-0565 AD - Kawasaki Medical School, Okayama, Japan. FAU - Okamoto, Taro AU - Okamoto T AUID- ORCID: 0000-0001-5494-462X AD - Japan Development, MSD K.K., Tokyo, Japan. FAU - Kameya, Miho AU - Kameya M AD - Japan Development, MSD K.K., Tokyo, Japan. FAU - Sato, Asako AU - Sato A AD - Japan Development, MSD K.K., Tokyo, Japan. FAU - Hirano, Tomona AU - Hirano T AD - Japan Development, MSD K.K., Tokyo, Japan. FAU - Oshima, Nobuyuki AU - Oshima N AD - Japan Development, MSD K.K., Tokyo, Japan. FAU - Gantz, Ira AU - Gantz I AUID- ORCID: 0000-0002-6565-7113 AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA. FAU - O'Neill, Edward A AU - O'Neill EA AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA. FAU - Engel, Samuel S AU - Engel SS AUID- ORCID: 0000-0002-4439-6356 AD - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA. CN - Omarigliptin Study 039 Group LA - eng SI - ClinicalTrials.gov/NCT02906709 GR - The study was funded and conducted by MSD K.K., Tokyo, Japan, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA./ GR - MSD K.K., Tokyo, Japan, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA./ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210217 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine) RN - 0 (Glycated Hemoglobin A) RN - 0 (Heterocyclic Compounds, 2-Ring) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Pyrans) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Glycated Hemoglobin MH - Glycemic Control MH - Heterocyclic Compounds, 2-Ring MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Insulin/adverse effects MH - Japan/epidemiology MH - Pyrans MH - Treatment Outcome PMC - PMC8248035 OTO - NOTNLM OT - MK-3102 OT - dipeptidyl peptidase-4 OT - incretins OT - insulin OT - once-weekly antihyperglycaemic agent OT - oral antihyperglycaemic agent COIS- TK has received contract research funds from AstraZeneca and Takeda; joint research funds from Daiichi Sankyo; grants from Astellas, Daiichi Sankyo, Eli Lilly, Kissei, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono, Sanofi, Sumitomo Dainippon, Taisho and Takeda; fees of consulting and/or lectures from Abbott, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Cosmic, Daiichi Sankyo, Eli Lilly, Fujifilm, Johnson & Johnson, Kissei, Kowa, Kyowa Hakko Kirin, Medical Review, Medical View, Medscape Education, Medtronic Sofamor Danek, Mitsubishi Tanabe, MSD, Musashino Foods, Nipro, Novartis, Novo Nordisk, Ono, Sanofi, Sanwa Kagaku, Sumitomo Dainippon, Taisho, Takeda and Terumo; and has been in an endowed chair from Asahi Mutual Life Insurance, Boehringer Ingelheim, Kowa, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono and Takeda. YS has received contracted/collaborative research funds from Bayer, Boehringer Ingelheim and Terumo; scholarship grants from Arklay, Novo Nordisk, Ono, Sumitomo Dainippon and Taisho Toyama; and fees of consulting and/or lectures from Becton Dickinson, Boehringer Ingelheim, Kao, MSD, Novo Nordisk, Taisho, Taisho Toyama and Takeda. KK has received scholarship grants from Boehringer Ingelheim, Daiichi Sankyo and Mitsubishi Tanabe; and fees of consulting and/or lectures from Astellas, AstraZeneca, Boehringer Ingelheim, Fujifilm, Kissei, Kowa, Mitsubishi Tanabe, MSD, Novartis, Novo Nordisk, Sanofi, Sanwa Kagaku, Sumitomo Dainippon, Taisho Toyama and Takeda. TO, MK, AS, TH, NO, IG, EAO'N and SSE are current employees of MSD K.K., Tokyo, Japan, or Merck Sharp & Dohme Corp., subsidiaries of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock/stock options in Merck & Co., Inc., Kenilworth, NJ, USA. No other potential conflicts of interest relevant to this article are reported. EDAT- 2021/01/30 06:00 MHDA- 2021/07/10 06:00 PMCR- 2021/07/01 CRDT- 2021/01/29 12:17 PHST- 2021/01/14 00:00 [revised] PHST- 2020/09/23 00:00 [received] PHST- 2021/01/23 00:00 [accepted] PHST- 2021/01/30 06:00 [pubmed] PHST- 2021/07/10 06:00 [medline] PHST- 2021/01/29 12:17 [entrez] PHST- 2021/07/01 00:00 [pmc-release] AID - DOM14331 [pii] AID - 10.1111/dom.14331 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Jun;23(6):1242-1251. doi: 10.1111/dom.14331. Epub 2021 Feb 17.